Sialic acids in infection and their potential use in detection and protection against pathogens.

In structural terms, the sialic acids are a large family of nine carbon sugars based around an alpha-keto acid core. They are widely spread in nature, where they are often found to be involved in molecular recognition processes, including in development, immunology, health and disease. The prominence of sialic acids in infection is a result of their exposure at the non-reducing terminus of glycans in diverse glycolipids and glycoproteins. Herein, we survey representative aspects of sialic acid structure, recognition and exploitation in relation to infectious diseases, their diagnosis and prevention or treatment. Examples covered span influenza virus and Covid-19, Leishmania and Trypanosoma, algal viruses, Campylobacter, Streptococci and Helicobacter, and commensal Ruminococci.

Targeted photodynamic therapy for breast cancer: the potential of glyconanoparticles.

Photodynamic therapy (PDT) uses a non-toxic light sensitive molecule, a photosensitiser, that releases cytotoxic reactive oxygen species upon activation with light of a specific wavelength. Here, glycan-modified 16 nm gold nanoparticles (glycoAuNPs) were explored for their use in targeted PDT, where the photosensitiser was localised to the target cell through selective glycan-lectin interactions. Polyacrylamide (PAA)-glycans were chosen to assess glycan binding to the cell lines. These PAA-glycans indicated the selective uptake of a galactose-derivative PAA by two breast cancer cell lines, SK-BR-3 and MDA-MD-231. Subsequently, AuNPs were modified with a galactose-derivative ligand and an amine derivate of the photosensitiser chlorin e6 was incorporated to the nanoparticle surface via amide bond formation using EDC/NHS coupling chemistry. The dual modified nanoparticles were investigated for the targeted cell killing of breast cancer cells, demonstrating the versatility of using glycoAuNPs for selective binding to different cancer cells and their potential use for targeted PDT.

Bilayer-Coating Strategy for Hydrophobic Nanoparticles Providing Colloidal Stability, Functionality, and Surface Protection in Biological Media.

The surface chemistry of nanoparticles is a key step on the pathway from particle design towards applications in biologically relevant environments. Here, a bilayer-based strategy for the surface modification of hydrophobic nanoparticles is introduced that leads to excellent colloidal stability in aqueous environments and good protection against disintegration, while permitting surface functionalization via simple carbodiimide chemistry. We have demonstrated the excellent potential of this strategy using upconversion nanoparticles (UCNPs), initially coated with oleate and therefore dispersible only in organic solvents. The hydrophobic oleate capping is maintained and a bilayer is formed upon addition of excess oleate. The bilayer approach renders protection towards luminescence loss by water quenching, while the incorporation of additional molecules containing amino functions yields colloidal stability and facilitates the introduction of functionality. The biological relevance of the approach was confirmed with the use of two model dyes, a photosensitizer and a nitric oxide (NO) probe that, when attached to the surface of the UCNPs, retained their functionality to produce singlet oxygen and detect intracellular NO, respectively. We present a simple and fast strategy to protect and functionalize inorganic nanoparticles in biological media, which is important for controlled surface engineering of nanosized materials for theranostic applications.

Gold nanoparticle-based two-photon fluorescent nanoprobe for monitoring intracellular nitric oxide levels.

Nitric oxide (NO) plays an important role in the regulation of the immune, cardiovascular and nervous systems. Consequently, being able to monitor and quantify intracellular NO levels would provide a greater understanding of the implications of this molecule in the different biological processes, including, for example, in cancer. Here, we report a broadly applicable two-photon excitable fluorescent nanoprobe able to detect and potentially quantify NO levels in an extensive range of cellular environments. The nanoprobe consists of a thiolated photoinduced electron transfer-based two=photon fluorescent probe attached onto the surface of 2.4 ± 0.7 nm gold nanoparticles (DANPY-NO@AuNPs). The nanoprobe, which can be synthesised in a reproducible manner and exhibits great stability when stored at room temperature, is able to selectively detect NO in solution, with a dynamic range up to 150 µM, and at pH values of biological relevance. DANPY-NO@AuNPs were able to selectively detect endogenous NO in RAW264.7γ NO- macrophages and THP-1 human leukemic cells; and endogenous and exogenous NO in endothelial cells. The nanoprobe accumulated in the acidic organelles of the tested cell lines showing negligible toxicity. Importantly, DANPY-NO@AuNPs showed potential to quantify intracellular NO concentrations in MDA-MB-231 breast cancer cells. The biological evaluation of the nanoprobe was undertaken using confocal laser scanning (images and intracellular emission spectra) and multiphoton microscopies, and flow cytometry. Based on their excellent sensitivity and stability, and outstanding versatility, DANPY-NO@AuNPs can be applied for the spatiotemporal monitoring of in vitro and in vivo NO levels.

Repercusiones de la COVID-19 en un proceso de investigación-acción participativa con adolescentes gitanas / Repercussions of COVID-19 in a participatory action-research process with adolescent Roma women

El objetivo de este artículo es describir la repercusión que ha tenido la pandemia de COVID-19 en la implementación del proyecto RoMoMatter, con una metodología de investigación-acción participativa basada en la comunidad, en Córdoba. Participaron cinco investigadoras académicas y 30 de la comunidad. Se utilizaron como técnicas de recogida de datos la entrevista individual, los grupos focales y las notas de campo. Las entrevistas fueron grabadas en audio con el consentimiento de las participantes y se transcribieron textualmente. La información recogida fue codificada mediante el software Atlas Ti. Se destacan los esfuerzos de adaptación al nuevo escenario de la pandemia realizados por las participantes y el papel de apoyo técnico y emocional que tuvo el equipo de adaptación. Se concluye que la principal repercusión de la pandemia se evidenció en el proceso participativo de todas las personas implicadas, y en el formato y el número de actividades.(AU)

The objective of this article is to describe the impact of the COVID-19 pandemic on the implementation of the RoMoMatter project, using a community-based participatory action research methodology, in Córdoba (Spain). Five academic researchers and 30 community members participated. Individual interviews, focus groups and field notes were used as data collection techniques. The interviews were audio-recorded with the consent of the participants and transcribed verbatim. The information collected was coded using Atlas Ti software. The efforts of adaptation to the new pandemic scenario made by the participants and the technical and emotional support role played by the adaptation team are highlighted. It is concluded that the main impact of the pandemic was evidenced in the participatory process of all the people involved, and in the format and number of activities. (AU)

[Repercussions of COVID-19 in a participatory action-research process with adolescent Roma women]. / Repercusiones de la COVID-19 en un proceso de investigación-acción participativa con adolescentes gitanas.

The objective of this article is to describe the impact of the COVID-19 pandemic on the implementation of the RoMoMatter project, using a community-based participatory action research methodology, in Córdoba (Spain). Five academic researchers and 30 community members participated. Individual interviews, focus groups and field notes were used as data collection techniques. The interviews were audio-recorded with the consent of the participants and transcribed verbatim. The information collected was coded using Atlas Ti software. The efforts of adaptation to the new pandemic scenario made by the participants and the technical and emotional support role played by the adaptation team are highlighted. It is concluded that the main impact of the pandemic was evidenced in the participatory process of all the people involved, and in the format and number of activities.

A highly photostable and versatile two-photon fluorescent probe for the detection of a wide range of intracellular nitric oxide concentrations in macrophages and endothelial cells.

Nitric oxide (NO) is involved in many biological processes affecting the cardiovascular, nervous and immune systems. Intracellular NO can be monitored using fluorescent probes in combination with fluorescence imaging techniques. Most of the currently available NO fluorescent molecular probes are excited via one-photon excitation using UV or Vis light, which results in poor penetration and high photodamage to living tissues. Here, we report a two-photon fluorescent molecular probe, DANPY-NO, able to detect NO in live cells. The probe consists of an o-phenylenediamine linked to a naphthalimide core; and operates via photoinduced electron transfer. DANPY-NO exhibits good sensitivity (LOD of 77.8 nM) and high selectivity towards NO, and is stable over a broad range of pHs. The probe targeted acidic organelles within macrophages and endothelial cells, and demonstrated enhanced photostability over a commercially available NO probe. DANPY-NO was used to selectively detect endogenous NO in RAW264.7ϒ NO- macrophages, THP-1 human leukemic cells, primary mouse (bone marrow-derived) macrophages and endothelial cells. The probe was also able to detect exogenous NO in endothelial cells and distinguish between increasing concentrations of NO. The NO detection was evidenced using confocal laser scanning and two-photon microscopies, and flow cytometry. Further evidence was obtained by recording the changes in the intracellular fluorescence emission spectrum of the probe. Importantly, the probe displayed negligible toxicity to the analysed biological samples. The excellent sensitivity, selectivity, stability and versatility of DANPY-NO confirm its potential for in vitro and in vivo imaging of NO.

Recent advances in near infrared upconverting nanomaterials for targeted photodynamic therapy of cancer.

Photodynamic therapy (PDT) is a well-established treatment of cancer that uses the toxic reactive oxygen species, including singlet oxygen (1O2), generated by photosensitiser (PS) drugs following irradiation of a specific wavelength to destroy the cancerous cells and tumours. Visible light is commonly used as the excitation source in PDT, which is not ideal for cancer treatment due to its reduced tissue penetration, and thus inefficiency to treat deep-lying tumours. Additionally, these wavelengths exhibit elevated autofluorescence background from the biological tissues which hinders optical biomedical imaging. An alternative to UV-Vis irradiation is the use of near infrared (NIR) excitation for PDT. This can be achieved using upconverting nanoparticles (UCNPs) functionalised with photosensitiser drugs where UCNPs can be used as an indirect excitation source for the activation of PS drugs yielding to the production of singlet1O2following NIR excitation. The use of nanoparticles for PDT is also beneficial due to their tumour targeting capability, either passivelyviathe enhanced permeability and retention (EPR) effect or activelyviastimuli-responsive targeting and ligand-mediated targeting (i.e.using recognition units that can bind specific receptors only present or overexpressed on tumour cells). Here, we review recent advances in NIR upconverting nanomaterials for PDT of cancer with a clear distinction between those reported nanoparticles that could potentially target the tumour due to accumulationviathe EPR effect (passive targeting) and nanoparticle-based systems that contain targeting agents with the aim of actively target the tumourviaa molecular recognition process.

Recent advances in nanoparticle-based targeting tactics for antibacterial photodynamic therapy.

The rise of antibacterial drug resistance means treatment options are becoming increasingly limited. We must find ways to tackle these hard-to-treat drug-resistant and biofilm infections. With the lack of new antibacterial drugs (such as antibiotics) reaching the clinics, research has switched focus to exploring alternative strategies. One such strategy is antibacterial photodynamic therapy (aPDT), a system that relies on light, oxygen, and a non-toxic dye (photosensitiser) to generate cytotoxic reactive oxygen species. This technique has already been shown capable of handling both drug-resistant and biofilm infections but has limited clinical approval to date, which is in part due to the low bioavailability and selectivity of hydrophobic photosensitisers. Nanotechnology-based techniques have the potential to address the limitations of current aPDT, as already well-documented in anti-cancer PDT. Here, we review recent advances in nanoparticle-based targeting tactics for aPDT.

Capacitación de población gitana en abogacía para la salud: un estudio de caso en Torreblanca, Sevilla / Training for Roma health advocacy: a case study of Torreblanca, Seville

Objetivo: El objetivo del presente estudio es crear capacidad de abogacía entre un grupo de vecinos/as gitanos/as que viven en contextos de riesgo de exclusión social. Método: Se ha utilizado un diseño de Investigación Acción Participativa Basada en la Comunidad, en el que el que 4 miembros de la comunidad participaron en el proceso de recogida de evidencias mediante fotovoz, análisis de estas siguiendo el método ReACT y diseminación de los resultados. Resultados: Se recogieron un total de 96 evidencias que fueron analizadas para el análisis de datos cualitativos. Estas fueron categorizadas atendiendo a (a) el tipo de condiciones insalubres y (b) la zona del barrio donde se encontraban. La posterior agrupación temática permitió identificar como causas: (a) El abandono de los servicios públicos; (b) la discriminación y (c) la falta de presencia de población gitana en los espacios comunitarios. Las consecuencias señaladas fueron (a) problemas de salud mental y física y (b) normalización de condiciones de vida indignas. El plan diseñado tuvo por objetivo abogar por la presencia gitana en los espacios comunitarios. Conclusiones: Nuestro estudio puso en evidencia la pertinencia del fotovoz para trascender la perspectiva biomédica y desarrollar acciones de abogacía basadas en el conocimiento creado por la comunidad. Futuras investigaciones deberían profundizar en el impacto de la abogacía para la salud en la reducción de las desigualdades y considerar la importancia de implicar a investigadores/as, profesionales de salud pública y la comunidad en su abordaj. (AU)

Objective: The objective of this study is to build advocacy capacity among a group of gipsy Roma neighbours living in contexts of risk of social exclusion. Methods: A Community Based Participatory Action Research design was used, in which 4 members of the community participated in the process of collecting evidence by photovoice, analysing it using the ReACT method and disseminating the results. Results: A total of 96 pieces of evidence were collected and analysed for qualitative data analysis. These were categorised according to (a) the type of unhealthy conditions and (b) the area of the neighbourhood where they were located. The subsequent thematic grouping made it possible to identify the causes: (a) the abandonment of public services; (b) discrimination; and (c) the lack of Roma presence in community spaces. The consequences identified were (a) mental and physical health problems and (b) the normalisation of undignified living conditions. The plan was designed to advocate for the presence of Roma in community spaces. Conclusions: Our study highlighted the relevance of the photovoice to transcend the biomedical perspective and develop advocacy actions based on the knowledge created by the community. Future research should look more deeply into the impact of health advocacy on reducing inequalities and consider the importance of involving researchers, public health professionals and the community in addressing it. (AU)

[Training for Roma health advocacy: a case study of Torreblanca, Seville]. / Capacitación de población gitana en abogacía para la salud: un estudio de caso en Torreblanca, Sevilla.

OBJECTIVE: The objective of this study is to build advocacy capacity among a group of gipsy Roma neighbours living in contexts of risk of social exclusion. METHODS: A Community Based Participatory Action Research design was used, in which 4 members of the community participated in the process of collecting evidence by photo-voice, analysing it using the ReACT method and disseminating the results. RESULTS: A total of 96 pieces of evidence were collected and analysed for qualitative data analysis. These were categorised according to (a) the type of unhealthy conditions and (b) the area of the neighbourhood where they were located. The subsequent thematic grouping made it possible to identify the causes: (a) the abandonment of public services; (b) discrimination; and (c) the lack of Roma presence in community spaces. The consequences identified were (a) mental and physical health problems and (b) the normalisation of undignified living conditions. The plan was designed to advocate for the presence of Roma in community spaces. CONCLUSIONS: Our study highlighted the relevance of the photo-voice to transcend the biomedical perspective and develop advocacy actions based on the knowledge created by the community. Future research should look more deeply into the impact of health advocacy on reducing inequalities and consider the importance of involving researchers, public health professionals and the community in addressing it.

Precious metal complexes of bis(pyridyl)allenes: synthesis and catalytic and medicinal applications.

The incorporation of donor-type substituents on the allene core opens up the possibility of coordination complexes in which the metal is bonded to the donor groups, with or without interaction with the double bond system. Despite the challenges in the synthesis of such allene-containing metal complexes, their unique 3D environments and dual functionality (allene and metal) could facilitate catalysis and interaction with chemical and biological systems. Bis(pyridyl)allenes are presented here as robust ligands for novel Pd(II), Pt(IV) and Au(III) complexes. Their synthesis, characterisation and first application as catalysts of benchmark reactions for Pd, Pt and Au are presented with interesting reactivity and selectivities. The complexes have also been probed as antimicrobial and anticancer agents with promising activities, and the first studies on their unusual interaction with several DNA structures will open new avenues for research in the area of metallodrugs with new mechanisms of action.

Recent Developments in the Use of Glyconanoparticles and Related Quantum Dots for the Detection of Lectins, Viruses, Bacteria and Cancer Cells.

Carbohydrate-coated nanoparticles-glyconanoparticles-are finding increased interest as tools in biomedicine. This compilation, mainly covering the past five years, comprises the use of gold, silver and ferrite (magnetic) nanoparticles, silicon-based and cadmium-based quantum dots. Applications in the detection of lectins/protein toxins, viruses and bacteria are covered, as well as advances in detection of cancer cells. The role of the carbohydrate moieties in stabilising nanoparticles and providing selectivity in bioassays is discussed, the issue of cytotoxicity encountered in some systems, especially semiconductor quantum dots, is also considered. Efforts to overcome the latter problem by using other types of nanoparticles, based on gold or silicon, are also presented.

Pulmonary-to-Systemic Arterial Shunt to Treat Children With Severe Pulmonary Hypertension.

BACKGROUND: The placement of a pulmonary-to-systemic arterial shunt in children with severe pulmonary hypertension (PH) has been demonstrated, in relatively small studies, to be an effective palliation for their disease. OBJECTIVES: The aim of this study was to expand upon these earlier findings using an international registry for children with PH who have undergone a shunt procedure. METHODS: Retrospective data were obtained from 110 children with PH who underwent a shunt procedure collected from 13 institutions in Europe and the United States. RESULTS: Seventeen children died in-hospital postprocedure (15%). Of the 93 children successfully discharged home, 18 subsequently died or underwent lung transplantation (20%); the mean follow-up was 3.1 years (range: 25 days to 17 years). The overall 1- and 5-year freedom from death or transplant rates were 77% and 58%, respectively, and 92% and 68% for those discharged home, respectively. Children discharged home had significantly improved World Health Organization functional class (P < 0.001), 6-minute walk distances (P = 0.047) and lower brain natriuretic peptide levels (P < 0.001). Postprocedure, 59% of children were weaned completely from their prostacyclin infusion (P < 0.001). Preprocedural risk factors for dying in-hospital postprocedure included intensive care unit admission (hazard ratio [HR]: 3.2; P = 0.02), mechanical ventilation (HR: 8.3; P < 0.001) and extracorporeal membrane oxygenation (HR: 10.7; P < 0.001). CONCLUSIONS: A pulmonary-to-systemic arterial shunt can provide a child with severe PH significant clinical improvement that is both durable and potentially free from continuous prostacyclin infusion. Five-year survival is comparable to children undergoing lung transplantation for PH. Children with severely decompensated disease requiring aggressive intensive care are not good candidates for the shunt procedure.

Non-Polymeric Nanogels as Versatile Nanocarriers: Intracellular Transport of the Photosensitizers Rose Bengal and Hypericin for Photodynamic Therapy.

The use of nanocarriers for intracellular transport of actives has been extensively studied in recent years and represents a central area of nanomedicine. The main novelty of this paper lies on the use of nanogels formed by a low-molecular-weight gelator (1). Here, non-polymeric, molecular nanogels are successfully used for intracellular transport of two photodynamic therapy (PDT) agents, Rose Bengal (RB) and hypericin (HYP). The two photosensitizers (PSs) exhibit different drawbacks for their use in clinical applications. HYP is poorly water-soluble, while the cellular uptake of RB is hindered due to its dianionic character at physiological pH values. Additionally, both PSs tend to aggregate precluding an effective PDT. Despite the different nature of these PSs, nanogels from gelator 1 provide, in both cases, an efficient intracellular transport into human colon adenocarcinoma cells (HT-29) and a notably improved PDT efficiency, as assessed by confocal laser scanning microscopy and flow cytometry. Furthermore, no significant dark toxicity of the nanogels is observed, supporting the biocompatibility of the delivery system. The developed nanogels are highly reproducible due to their non-polymeric nature, and their synthesis is easily scaled up. The results presented here thus confirm the potential of molecular nanogels as valuable nanocarriers, capable of entrapping both hydrophobic and hydrophilic actives, for PDT of cancer.

Active targeting of gold nanoparticles as cancer therapeutics.

Gold nanoparticles (AuNPs) are of increasing interest for their unique properties and their biocompatability, minimal toxicity, multivalency and size tunability make them exciting drug carriers. The functionalisaton of AuNPs with targeting moieties allows for their selective delivery to cancers, with antibodies, proteins, peptides, aptamers, carbohydrates and small molecules all exploited. Here, we review the recent advances in targeted-AuNPs for the treatment of cancer, with a particular focus on these classes of targeting ligands. We highlight the benefits and potential drawbacks of each ligand class and propose directions in which the field could grow.

Building Meaningful Community Advocacy for Ethnic-based Health Equity: The RoAd4Health Experience.

The pervasive failure of policies aimed at overcoming health inequities suffered by European Roma reflects the oppressive and impoverished living conditions of many ethnic minorities in the Western world. The multiple social inequities that Roma experience and the cumulative effect on their health prove that the failure of health policies that impact Roma must be attributed to their ameliorative nature. These policies legitimize the mechanisms of oppression that sustain inequities, fueling fatalistic attitudes toward minorities, while these minorities internalize the stigma and attempt to survive on the margins of society. This paper presents the RoAd4Health project, a community initiative in which academic researchers partnered with Roma communities to overcome health inequities. We present the multiple methods utilized for building meaningful advocacy, such as photovoice and asset mapping led by Roma agents of change. These methods provided the capacity to develop a local narrative of disparities, build alliances to gain capacity to respond to injustices, and take actions to promote social change. The results of effectively involving all significant stakeholders (i.e., community agents of change, residents, health and social care providers, Roma community grassroots organizations, and institutional actors) are discussed along with lessons learned.

RoMoMatteR: Empowering Roma Girls' Mattering through Reproductive Justice.

Aim: To present a protocol study directed at tackling gender discrimination against Roma girls by empowering their mattering so they can envision their own futures and choose motherhood only if-and when-they are ready. Background: Motherhood among Roma girls (RGM) in Europe impoverishes their lives, puts them at risk of poor physical and mental health and precipitates school dropouts. Overwhelming evidence affirms that the conditions of poverty and the social exclusionary processes they suffer have a very important explanatory weight in their sexual and reproductive decisions. Methods: Through a Community-based Participatory Action Research design, 20-25 Roma girls will be recruited in each one of the four impoverished communities in Bulgaria, Romania and Spain. Data collection and analysis: Desk review about scientific evidences and policies will be carried out to frame the problem. Narratives of Roma women as well as baseline and end line interviews of girl participants will be collected through both qualitative and quantitative techniques. Quantitative data will be gathered through reliable scales of mattering, socio-political agency, satisfaction with life and self. A narrative analysis of the qualitative information generated in the interviews will be carried out. Expected results: (1) uncover contextual and psychosocial patterns of girl-motherhood among Roma women; (2) build critical thinking among Roma girls to actively participate in all decisions affecting them and advocate for their own gender rights within their communities; and (3) empower Roma girls and their significant adults to critically evaluate their own initiatives and provide feedback to their relevant stakeholders. Conclusions: Roma girls will improve their educational aspirations and achievements and their social status while respecting and enhancing Roma values.

Peptide directed phthalocyanine-gold nanoparticles for selective photodynamic therapy of EGFR overexpressing cancers.

Gold nanoparticles, covalently functionalised with the photosensitiser C11Pc and PEG, were actively targeted towards epidermal growth factor receptor overexpressing cancers using the peptide FITC-ßAAEYLRK. Selective phototoxicity was observed at nanomolar concentrations with minimal dark toxicity.

Aptamer-modified gold nanoparticles for rapid aggregation-based detection of inflammation: an optical assay for interleukin-6.

A proof-of-concept aptamer-based optical assay is described for the determination of the immuno signalling molecule interleukin-6 (IL-6), a key marker of acute inflammation. The optical assay is based on the aggregation of gold nanoparticles (AuNP) coated in two complimentary "sandwich-style" aptamers, each with different IL-6 target moieties. IL-6 will recognise the complimentary aptamer pair and bind to it, thereby causing the aggregation of the corresponding functionalised nanoparticles. The aggregation of the AuNPs after exposure to IL-6 induces a visible colour change from red to pink, with a corresponding change in the absorption maximum from 520 to 540 nm. The change in the absorption maximum can be monitored visually, or by using a spectrophotometer or a plate reader. The optimal size and functionalisation of aptamer-coated AuNPs, and the potential assay formats were investigated using UV-vis spectrophotometry, transmission electron microscopy, and dynamic light scattering. The optical assay was applied for detecting mouse IL-6 in a mixed protein solution as a representative biological sample. The assay works in the 3.3 to 125 µg·mL-1 IL-6 concentration range, and the detection limit (at S/N = 3) is 1.95 µg·mL-1. This study was performed as a proof-of-concept demonstration of this versatile assay design, with a view to developing a similar assay for use in clinical samples in future. Graphical abstractSchematic representation of the aggregation of aptamer-functionalised nanoparticles in the presence of interleukin-6 (IL-6). The presence of mouse IL-6 in a mixed protein solution leads to a visible colour change, and a change in the absorption spectrum of the nanoparticles.